Two Cases Link Painkiller to Risk of Suicide

The painkiller ziconotide (Prialt) may cause an increase in suicidal ideation, experts warned.

The painkiller ziconotide (Prialt) may cause an increase in suicidal ideation, experts warned.

Two recent cases "substantiate the suspicion of a causal relationship between ziconotide and suicidality," reported Christoph Maier, MD, of the Ruhr University in Bochum, Germany, and colleagues.

Because of the risk, patients should undergo a comprehensive psychiatric evaluation before and during treatment with the drug, Maier and colleagues argued online in Pain.

Ziconotide, a synthetic version of a toxin derived from a marine snail, was approved in the U.S. in 2004 on the basis of an orphan drug designation. Delivered intrathecally, it was regarded as a safe alternative to morphine in cases of severe pain that did not respond to other medications.

However, neurological and psychiatric complications including ataxia, gait disturbances, confusion, and abnormal thinking have been reported and have led to a black box warning ordered by the FDA, although no such warning has been issued in Europe, Maier and colleagues noted.

But there has been no specific warning on an increased risk of suicide, they reported.

The two cases, however, support "the suspicion of ziconotide-induced suicidality," they argued.

In the first case, a 66-year-old man with severe foot pain was treated with the drug after other pain medications proved inadequate, the researchers reported. Two years before, his doctors had considered the possibility of depression, but the diagnosis was not supported by a psychiatric assessment.

Indeed, when the patient was admitted to the pain clinic two months before ziconotide treatment, he had only slightly elevated anxiety and depression subscores on the Hospital Anxiety and Depression Scale and a psychological evaluation showed no sign of depressive disorder other than sleep disturbance, which was blamed on pain, the researchers reported.

Ziconotide was started at 0.5 micrograms a day, with a stepwise increase of the dose during the following nine days to 1.2 micrograms daily and eventually increased to 4.4 micrograms a day without side effects, they reported.

The man's scores on the Hospital Anxiety and Depression Scale fell and he showed no signs of suicidal ideation at a clinic visit to refill the pump, Maier and colleagues said.

But eight weeks after starting therapy, he was found hanged. His widow reported he had appeared quite happy during the previous two weeks, but had -- for the first time -- expressed suicidal ideas.

The second patient was a 39-year-old woman with a history of depression and 14 years of pain treatment for backache.

Maier and colleagues reported she was admitted to their clinic after six months of treatment with ziconotide that had been started -- contrary to current recommendations -- at another pain clinic.

She said the drug was not easing her pain, and she reported increasing cognitive and psychiatric symptoms, including general restlessness, severe sleep disturbance, salty taste sensation, nausea, rotatory vertigo, reduced appetite, and increasing suicidal ideation, according to the researchers.

She was also severely depressed, with a score of 30 on the Hamilton Depression Scale.

Stopping the ziconotide led to a moderate recovery from the depression -- the Hamilton score fell to 22 -- and a remission of suicidal ideation after 14 days.

Taken together, the two cases raise the concern that the drug causes suicidality, Maier and colleagues concluded.

On one hand, they argued, the suicidal ideation began only after the drug was started and neither patient had depressive symptoms at the time. On the other hand, in the female patient, stopping the drug immediately eliminated the suicidal thoughts, as well as the other psychiatric symptoms.

Maier and colleagues urged that patients considered for treatment with the drug should first get a thorough psychiatric assessment and, once treatment is started, they should be monitored closely for depressive symptoms and suicidal ideation.

The researchers did not report external support for the study. They reported that they had no financial or other relationships that might lead to a conflict of interest.

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